The principal goal of this proposal is to elucidate pathogenic mechanisms in immunologically mediated tubular and interstitial renal disease in experimental animals and in man. The model of anti tubular basement membrane disease (antiTBM disease) will be studied with respect to the role of antibody mediated cytotoxic tubular damage, the nature and function of the infiltrating mononuclear cells and the role of the clotting system. A radioimmunoassay method for measuring circulating human antiTBM antibodies will be developed and used to assess the importance of such antibodies in various forms of tubulointerstitial disease, including drug induced interstitial nephritis and in renal allograft recipients. The nature of the antigen(s) with which human antiTBM and antiGBM antibodies react will be studied. The conditions required for the elicitation of delayed hypersensitivity reactions in the renal interstitium will be studied, with particular attention to the physical state of the antigen. The structural and immunopathologic features of various forms of tubulointerstitial renal disease in man will be investigated through characterization of the infiltrating cells by morphologic and immunologic techniques, and through detection of in vivo bound antiTBM antibodies or immune complex deposition. The clinical and functional significance of these lesions will be studied.